Antonino Naro

Robotic gait rehabilitation and substitution devices in neurological disorders: where are we now?

Gait abnormalities following neurological disorders are often disabling, negatively affecting patients’ quality of life. Therefore, regaining of walking is considered one of the primary objectives of the rehabilitation process. To overcome problems related to conventional physical therapy, in the last years there has been an intense technological development of robotic devices, and robotic rehabilitation has proved to play a major role in improving one’s ability to walk. The robotic rehabilitation systems can be classified into stationary and overground walking systems, and several studies have demonstrated their usefulness in patients after severe acquired brain injury, spinal cord injury and other neurological diseases, including Parkinson’s disease, multiple sclerosis and cerebral palsy. In this review, we want to highlight which are the most widely used devices today for gait neurological rehabilitation, focusing on their functioning, effectiveness and challenges. Novel and promising rehabilitation tools, including the use of virtual reality, are also discussed.

Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients

PURPOSE Disorders of consciousness (DOC) diagnosis relies on the presence or absence of purposeful motor responsiveness, which characterizes the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS), respectively. Functional neuroimaging studies have raised the question of possible residual conscious awareness also in clinically-defined UWS patients. The aim of our study was to identify electrophysiological parameters, by means of a transcranial magnetic stimulation approach, which might potentially express the presence of residual networks sustaining fragmentary behavioral patterns, even when no conscious behavior can be observed. METHODS We enrolled 25 severe DOC patients, following post-anoxic or traumatic brain injury and 20 healthy individuals (HC) as control group. Baseline electrophysiological evaluation evidenced, in comparison to HC, a partial preservation of cortical effective connectivity and excitability in clinically defined MCS, whereas these components were absent in clinically defined UWS. Then, we applied an anodal transcranial direct current stimulation (a-tDCS) protocol over the orbitofrontal cortex. RESULT a-tDCS was able to boost cortical connectivity and excitability in all HC, MCS, and to unmask such excitability/connectivity in some UWS patients. CONCLUSION a-tDCS could be useful in identifying residual connectivity markers in clinically-defined UWS, who may lack of purposeful behavior as a result of a motor-output failure.

A Single Session of Repetitive Transcranial Magnetic Stimulation Over the Dorsolateral Prefrontal Cortex in Patients With Unresponsive Wakefulness Syndrome: Preliminary Results.

Background. The level of consciousness is regulated by the activation of the frontal parietal network since a disruption within this interregional cortical connectivity is associated with a consciousness breakdown. Objective. The primary aim of the present study was to examine the feasibility and the safety of a single session of repetitive transcranial magnetic stimulation (rTMS), delivered over the dorsolateral prefrontal cortex (DLPFC), in patients with unresponsive wakefulness syndrome (UWS). As a secondary aim, we investigated the efficacy of rTMS over DLPFC on cortico-cortical connectivity as tested with paired-pulse and dual-coil TMS techniques. Methods. We enrolled 10 healthy and 10 postanoxic UWS subjects. After clinical assessment, subjects underwent a single/paired pulse TMS paradigm evaluating the inhibitory and facilitatory intracortical circuits. In addition, several interregional interactions between primary motor, dorsal and ventral premotor, supplementary motor, and posterior parietal cortex areas were investigated by means of dual-coil TMS technique. These parameters were evaluated at baseline, immediately after, and 60 minutes after a protocol of 10-Hz rTMS delivered at the level of the DLPFC. Results. rTMS over DLPFC did not cause any adverse events. We showed that rTMS over DLPFC did not induce, at group level, any clinical improvement or intra-/intercortical connectivity changes. Interestingly, in 3 patients rTMS induced a significant, although transient, clinical improvement associated with a short-lasting reshaping of brain connectivity. Conclusions. We demonstrated that a single session of 10-Hz rTMS over the right DLPFC may transiently improve consciousness and partially restore the connectivity within several cortical areas in some patients with UWS.

Cortical connectivity modulation induced by cerebellar oscillatory transcranial direct current stimulation in patients with chronic disorders of consciousness: A marker of covert cognition?

OBJECTIVE Although some patients suffering from unresponsive wakefulness syndrome (UWS) may retain some capacity for covert cognition, it is difficult to directly demonstrate this property by means of tasks needing patient active cooperation and preserved top-down attention processes. Instead, specific passive paradigms may allow identifying a residual θ and γ band functional connectivity within fronto-parietal networks (FPN), which may sustain covert cognitive processes. METHODS We attempted to highlight such networks in a sample of minimally conscious state (MCS) and UWS patients by means of a cerebellar 5 Hz oscillatory transcranial direct current stimulation (otDCS), in order to modulate the FPN functional connectivity. RESULTS We found a FPN θ and γ power modulation and coherence increase, which were paralleled by a transient coma recovery scale-revised score amelioration, only in MCS individuals. CONCLUSIONS Our data show a functional link between the FPN coherent θ and γ oscillations and the cerebellar-cerebral output. Moreover, our data highlighted a residual FPN functional connectivity, which is a fundamental prerequisite for objectifying every aware processes and the potential to cognitive processes (covert cognition). SIGNIFICANCE Our otDCS cerebellar-cerebral connectivity modulation may be a useful approach in improving chronic disorders of consciousness differential diagnosis and ameliorating the level of consciousness.

Sativex in the Management of Multiple Sclerosis-Related Spasticity: Role of the Corticospinal Modulation

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and Hmax/Mmax ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability.

Protracted exercise without overt neuromuscular fatigue influences cortical excitability.

ABSTRACT The authors’ aim was to determine the cortical mechanisms that underlie the transition from effective performance to its disruption. They thus used transcranial magnetic stimulation (TMS) to study changes of corticospinal excitability after a motor exercise that did not produce overt or perceived neuromuscular fatigue. Forty-four subjects performed either 5 or 10 min of repetitive finger movements paced by tones at 2 Hz, a frequency below the spontaneous movement rate. Changes of corticospinal excitability were assessed with TMS at rest and during motor response preparation (premovement facilitation paradigm). Over time, variability of movement rate increased, while the average movement rate shifted toward self-paced rhythms, without significant changes in other kinematic parameters. Amplitudes of motor evoked potentials at rest decreased depending on task duration and TMS intensity. Moreover, 5-min exercise induced fully compensatory increases in premovement facilitation, while 10-min exercise produced partially compensatory increases with loss of temporal modulation. Our findings suggest that protracted exercise induces significant decrements in corticospinal excitability with initial impairment of the phasic motor neurons that are recruited at higher stimulus intensities. Changes in premovement facilitation likely represent compensation of premotor areas for decreased efficiency of the primary motor cortex induced by exercise.

Evaluating Sativex® in Neuropathic Pain Management: A Clinical and Neurophysiological Assessment in Multiple Sclerosis

OBJECTIVE The aim of our study was to better investigate the role of Sativex(®) in improving pain in multiple sclerosis (MS) patients by means of either clinical or neurophysiological assessment. SETTING Pain is a common symptom of MS, affecting up to 70% of patients. Pain treatment is often unsatisfactory, although emerging drugs (including cannabinoids) are giving encouraging results. Clinical pain assessment in MS is very difficult, and more objective tools are necessary to better quantify this symptom and its potential response to the treatments. SUBJECTS AND METHODS We enrolled 20 MS patients (10 with and 10 without neuropathic pain), who underwent a specific clinical (such as visual analog scale) and neurophysiological assessment (by means of laser-evoked potentials and transcranial magnetic stimulation), before and after 4 weeks of Sativex administration. RESULTS One month of drug administration in MS patients with neuropathic pain successfully reduced pain rating and improved quality of life. Interestingly, such effects were paralleled by an increase of fronto-central γ-band oscillation and of pain-motor integration strength. CONCLUSIONS Our data suggest that Sativex may be effective in improving MS-related neuropathic pain, maybe through its action on specific cortical pathways.

Who May Benefit From Armeo Power Treatment? A Neurophysiological Approach to Predict Neurorehabilitation Outcomes

The Armeo Power, a rehabilitation exoskeleton that allows early treatment of motor disabilities, provides intelligent arm support in a large 3‐dimensional work space, thus enabling patients to perform intensive, repetitive, and goal‐oriented exercises. This device could efficiently induce new connections and facilitate plasticity phenomena potentiation. Knowledge of the potential brain plasticity reservoir after brain damage constitutes a prerequisite for an optimal rehabilitation strategy.

Associative cortico-cortical plasticity may affect ipsilateral finger opposition movements.

We have recently demonstrated that cortico-cortical paired associative stimulation (cc-PAS) can modulate interhemispheric inhibition (IHI) in the human brain. Here we further explored the after effects of cc-PAS on fine hand movements. Ten healthy right-handed volunteers received 90 paired transcranial stimuli to the right and left primary motor hand area (M1(HAND)) at an interstimulus interval (ISI) of 8 ms. We studied the after effects of cc-PAS on the performance of repetitive finger opposition movements of different complexity on both hands using a sensor-engineered glove. A quantitative evaluation of the following parameters was performed: Touch Duration (TD), Inter Tapping Interval (ITI) and Number of Errors (NE). We confirmed previous data by showing that left-to-right and right-to-left cc-PAS attenuated IHI. The new finding is that both left-to-right and right-to-left cc-PAS were able to influence the performance of a simple finger opposition movement changing the duration of TD and ITI. Interestingly the effect on the two hands was opposite in direction. These results provide further insight that cc-PAS can induce associative plasticity in connections between the targeted cortical areas influencing motor hand performances. These results may be relevant for future rehabilitative applications.

Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand

Movement disorders associated with complex regional pain syndrome type I have been a subject of controversy over the last 10 years regarding their nature and pathophysiology, with an intense debate about the functional (psychogenic) nature of this disorder. The aim of this study was to test sensorimotor plasticity and cortical excitability in patients with complex regional pain syndrome type I who developed a fixed posture of the hand.